DNA adducts: endogenous and induced

Abstract

Human exposure to DNA damaging agents can arise from exogenous sources or endogenous processes that occur normally or in pathological states. DNA isolated from human tissues, obtained from the very young to the old, contains detectable amounts of a number of different types of DNA adducts that reflect exposure to both known carcinogens and as yet unidentified genotoxic agents. The levels of DNA damage observed in human studies as a result of exogenous exposures (noniatrogenic) is of the order of 1 adduct per 10(7)-10(9) normal DNA bases, whereas that arising from endogenous exposures may potentially be several orders of magnitude higher. Large interindividual variations in DNA adduct levels have been reported, and these are probably the result of host and environmental factors, although variation in analytical and sampling procedures may also play a role. It is important to recognize that the presence of DNA adducts in a tissue does not necessarily indicate a specific tumorigenic risk for that tissue, as other factors downstream of DNA adduct formation (including DNA repair and cell proliferation) play an important role in determining overall risk.